Dr Paul A Clarke

Natural Products, Medicinal Chemistry and Origins of Life

Research in the group focuses on the total synthesis of biologically active natural products, the development of new routes to 3D-molecular scaffolds for use in drug discovery, and the prebiotic genesis of sugars, glycolipids and inorganic phosphate.

The group has expertise in the development of new methods for the formation of tetrahydropyran units, using both the Maitland-Japp reaction and a stereodivergent oxy-Michael reaction. This has enabled us to synthesise a number of natural products including centrolobine and diospongin A and B. These reactions are being applied to the synthesis of larger natural products such as phorboxazole B. Also under investigation are applications of the Diels-Alder reaction to the synthesis of the core structural units present in natural products like anthracimycin.

We are also interested in the development of new routes to 3D-spirocyclic and bridged heterocyclic scaffolds for use in drug discovery programs. Specifically, we have devised new routes to the under-represented 2-spiropiperidine class of scaffold, and have developed some simple reactions to transform these into 3D-scaffolds with a high lead-likeness.

The group has an interest in applying synthetic techniques to investigate the origins of Life. We are investigating the synthesis of “living protocells” as vehicles for the generation of important prebiotic building blocks, carbohydrates, glycolipids and inorganic phosphate.